Therapeutic Drug Monitoring Flashcards
Therapeutic drug monitoring is defined as…
“a process of assessing concentration of a drug in biological fluids such that it is maintained within the therapeutic range.”
Therapeutic drug monitoring aims at…
…individualizing the dose for a patient to obtain maximum benefit.
Therapeutic drug monitoring (TDM) is generally defined as the clinical…
…laboratory measurement of a chemical parameter that, with appropriate medical interpretation, will directly influence drug prescribing procedures.
TDM involves the use of drug concentration…
…measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease.
The main focus of TDM is…
…drugs with a narrow therapeutic range i.e. drugs that can easily be under- or overdosed.
TDM is based on the principle that…
…for some drugs, there is a close relationship between the plasma level of the drug and its clinical effect.
The clinical value of plasma level monitoring depends on…
…how precisely the treatment outcome can be defined
The therapeutic range/ therapeutic window is…
… the concentration range of drug in plasma where the drug has been shown to be efficacious without causing toxic effects in most people.
Therapeutic Index (TI) refers to…
…the ratio of the dose of drug that causes adverse effects at an incidence/severity not compatible with the targeted indication (e.g. toxic dose in 50% of subjects, TD50) to the dose that leads to the desired pharmacological effect (e.g. efficacious dose in 50% of subjects, ED50).
In a drug development setting, TI is calculated based on…
…plasma exposure levels
Therapeutic index = LD50 x ED50. True or false?
False. It’s division, not multiplication
Criteria for TDM in drugs
- Unpredictable relationship between dose and plasma
- Narrow therapeutic window
- Steep dose response curve
- Difficult-to-measure therapeutic/toxic evidence
- Saturable metabolism
- Poorly defined endpoint/response
Features of drugs with narrow therapeutic window
They allow dosage alterations to produce optimal therapeutic effect
TDM is not useful in…
- Drugs having wide therapeutic index
- Where toxicity is not a realistic concern
- Effects can be measured using functional laboratory tests
- Plasma concentration not predictably related to effects
- Hit and run drugs
Components of an optimum TDM service
- Timely measurement of patient’s serum or plasma drug concentration
- Knowledge of pharmacological and pharmacokinetic profiles of the drugs
- Knowledge of relevant patient’s profile
- Interpretation of SDC after taking into consideration all of the above information
Processes involved in TDM
- Development of plasma profile
- Clinical effect of drug
- Development of dosage regimen
- Diagnosis, dosage form selection, dosage regimen, initiation of therapy
- Evaluation of clicinical response
Sample selection must include
…an appropriate matrix.
Samples used for drug assays
Plasma
Whole blood
Saliva
Storage of samples:
Plastic cryovial type tubes are acceptable for most assays
Measures before collecting the sample
- Establish that serum-drug concentration (SDC) is at steady-state
- Ensure complete absorption and distribution
- Samples should be collected and centrifuged as soon as possible.
Serum-separator tubes should be avoided because
these may lower drug concentrations due to the adsorption of drug into the matrix
For adequate absorption and therapeutic levels to be accurate, it is important to allow for little time to pass between the administration of the medication and the collection of the blood sample. True or false?
False. Sufficient time should pass.
Blood specimens for drug monitoring can be taken at two different times:
- During the drug ́s highest therapeutic concentration (‘peak’ level)
- It’s lowest (‘trough’ level).
Trough levels show
sufficient therapeutic levels
Peak levels show
…toxicity
Patients receiving a drug at a dosing interval longer than the half-life of the drug will demonstrate…
…large fluctuations between peak and trough levels.
Plasma concentrations of drugs dosed at intervals shorter than their half-lives would show…
… less fluctuation between peak and trough levels
For chronically administered oral medications the peak levels usually occur…
…1-2 hours after the dose and the trough serum concentration, shortly after the dose is administered.
In Digoxin, the serum level to determine peak activity should be drawn…
…after the serum digoxin has had time to equilibrate with the tissue i.e., 6-10 hours after the oral dose.
Intravenous medications should drawn…
…after being given time to equilibrate before the peak level is drawn. They should be sampled 1⁄2-1 hour after administration
For patients suspected of symptoms of drug toxicity, the best time to draw the blood specimen is…
… when the symptoms are occurring; i.e., immediately at the time of presentation.
Medications that are poorly soluble at body pH have what kind of serum level?
Low and late peak serum levels because they may precipitate at the site of injection
What are therapeutic ranges?
These are the recommendations derived by observing the clinical responses of a small group of patients taking the drug.
The lower and upper limits of the therapeutic range are set to provide…
…~50% of the maximum therapeutic effect for lower, while the upper limit is defined by toxicity.
Factors affecting results of TDM testing
- Pharmacokinetics
- Pharmacodynamics
- Dose
- Sampling time and type
- Testing methodology
- Genetic polymorphisms
- Drug formulation and circadian effect
- Use of Alternative system of medicine.
Major sources of pharmacokinetic variation
- Patient Compliance – lack of
- Age
- Physiology – gender, pregnancy
- Disease
- Drug-to-drug interactions
- Environmental influences
Pharmacokinetic parameters that are important in therapeutic drug monitoring include:
i. Bioavailability.
ii. Volume of distribution and distribution phases.
iii. Clearance
iv. Half-life
v. Protein binding of drugs
The least variable concentrations, most often used to establish therapeutic ranges are…
Trough values
Factors that affect interpretation of TDM
- Protein Binding
- Steady State
- Active Metabolites
Techniques for TDM measurement
- HPLC: High Pressure Liquid Chromatography
- LC/MS: Liquid Chromatography Mass Spectrometry
- GC/MS: Gas chromatography
- EIA: Enzyme immunoassay
- PETINIA: Particle Enhanced Turbidimetric Inhibition Immunoassay
- EMIT: Enzyme Multiplied Immunoassay Technique
- Chemiluminescence
- ACMIA: Affinity Chrome-Mediated Immunoassay
Clinical significance of TDM
- Maximizes efficacy
- Avoids toxicity
- Identifies therapeutic failure
- Greater insight into factors determining patient response to drug therapy
- Facilitates the therapeutic effect of drug by achieving target drug concentration
- Identify poisoning, drug toxicity and drug abuse
